期刊
CANCER RESEARCH
卷 72, 期 11, 页码 2757-2767出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-11-3379
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资金
- INCa
- ANR
- Ligue contre le cancer
- INFLACARE EU grant
- Canceropole IDF
- Ligue Nationale contre le Cancer
- Deutsche Forschungsgemeinschaft (DFG)
- Deutsche Krebshilfe (German Cancer Aid)
- ELAN
- IZKF program of the University Erlangen, Germany
- Institut National du Cancer (INCa)
- Association pour la Recherche sur le Cancer (ARC)
- Grants-in-Aid for Scientific Research [22240089] Funding Source: KAKEN
During cancer development, a number of regulatory cell subsets and immunosuppressive cytokines subvert adaptive immune responses. Although it has been shown that tumor-derived interleukin (IL)-18 participates in the PD-1-dependent tumor progression in NK cell-controlled cancers, the mechanistic cues underlying this immunosuppression remain unknown. Here, we show that IL-18 converts a subset of Kit(-) (CD11b(-)) into Kit(+) natural killer (NK) cells, which accumulate in all lymphoid organs of tumor bearers and mediate immunoablative functions. Kit(+) NK cells overexpressed B7-H1/PD-L1, a ligand for PD-1. The adoptive transfer of Kit(+) NK cells promoted tumor growth in two pulmonary metastases tumor models and significantly reduced the dendritic and NK cell pools residing in lymphoid organs in a B7-H1-dependent manner. Neutralization of IL-18 by RNA interference in tumors or systemically by IL-18-binding protein dramatically reduced the accumulation of Kit(+)CD11b(-) NK cells in tumor bearers. Together, our findings show that IL-18 produced by tumor cells elicits Kit(+)CD11b(-) NK cells endowed with B7-H1-dependent immunoablative functions in mice. Cancer Res; 72(11); 2757-67. (C)2012 AACR.
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